Correction: Effects of chronic exposure to arsenic on the fecal carriage of antibiotic-resistant Escherichia coli among people in rural Bangladesh.

[This corrects the article DOI: 10.1371/journal.ppat.1010952.].

Effects of chronic exposure to arsenic on the fecal carriage of antibiotic-resistant Escherichia coli among people in rural Bangladesh.

Antibiotic resistance is a leading cause of hospitalization and death worldwide. Heavy metals such as arsenic have been shown to drive co-selection of antibiotic resistance, suggesting arsenic-contaminated drinking water is a risk factor for antibiotic resistance carriage. This study aimed to determine the prevalence and abundance of antibiotic-resistant Escherichia coli (AR-Ec) among people and drinking water in high (Hajiganj, >100 µg/L) and low arsenic-contaminated (Matlab, <20 µg/L) areas in Bangladesh. Drinking water and stool from mothers and their children (<1 year) were collected from 50 households per area. AR-Ec was detected via selective culture plating and isolates were tested for antibiotic resistance, arsenic resistance, and diarrheagenic genes by PCR. Whole-genome sequencing (WGS) analysis was done for 30 E. coli isolates from 10 households. Prevalence of AR-Ec was significantly higher in water in Hajiganj (48%) compared to water in Matlab (22%, p <0.05) and among children in Hajiganj (94%) compared to children in Matlab (76%, p <0.05), but not among mothers. A significantly higher proportion of E. coli isolates from Hajiganj were multidrug-resistant (83%) compared to isolates from Matlab (71%, p <0.05). Co-resistance to arsenic and multiple antibiotics (MAR index >0.2) was observed in a higher proportion of water (78%) and child stool (100%) isolates in Hajiganj than in water (57%) and children (89%) in Matlab (p <0.05). The odds of arsenic-resistant bacteria being resistant to third-generation cephalosporin antibiotics were higher compared to arsenic-sensitive bacteria (odds ratios, OR 1.2-7.0, p <0.01). WGS-based phylogenetic analysis of E. coli isolates did not reveal any clustering based on arsenic exposure and no significant difference in resistome was found among the isolates between the two areas. The positive association detected between arsenic exposure and antibiotic resistance carriage among children in arsenic-affected areas in Bangladesh is an important public health concern that warrants redoubling efforts to reduce arsenic exposure.

Dynamics of a stage-structured predator-prey system with fear-induced group defense in autonomous and nonautonomous settings.

In this investigation, we construct a predator-prey model that distinguishes between immature and mature prey, highlighting group defense strategies within the mature prey. First, we embark on exploring the positivity and boundedness of the solution, unraveling sustainable equilibrium points, and deducing their stability conditions. Upon further investigation, we observe that the system exhibits diverse bifurcations, including Hopf, saddle-node, transcritical, generalized Hopf, cusp, and Bogdanov-Takens bifurcations. The results reveal that heightened fear decreases mature prey density, potentially causing prey extinction beyond a certain threshold. Increased maturation rates lead to the coexistence of immature and mature prey populations and higher predator density. Stronger group defense boosts mature prey density, while weaker defense results in weak persistence. Lower values of the maturation rate of prey and the decline rate of predators sustain only the predator population, reliant on resources other than focal prey. Furthermore, our model demonstrates intriguing and diverse dynamical phenomena, including various forms of bistability across distinct bi-parameter planes. We also explore the dynamics of a related nonautonomous system, where certain parameters are considered to vary with time. In the seasonally forced model, we set out to define criteria regarding the existence and stability of positive periodic solutions. Numerical investigations into the seasonally forced model uncover a spectrum of dynamics, ranging from simple periodic solutions to higher periodicities, bursting patterns, and chaotic behavior.

Bifurcation analysis of autonomous and nonautonomous modified Leslie-Gower models.

In ecological systems, the predator-induced fear dampens the prey's birth rate; yet, it fails to extinguish their population, as they endure and survive even under significant fear-induced costs. In this study, we unveil a modified Leslie-Gower predator-prey model by incorporating the fear of predators, cooperative hunting, and predator-taxis sensitivity. We embark upon an exploration of the positivity and boundedness of solutions, unearthing ecologically viable equilibrium points and their stability conditions governed by the model parameters. Delving deeper, we unravel the scenario of transcritical, saddle-node, Hopf, Bogdanov-Takens, and generalized-Hopf bifurcations within the system's intricate dynamics. Additionally, we observe the bistable nature of the system under some parametric conditions. Further, the nonautonomous extension of our model introduces the intriguing interplay of seasonality in some crucial parameters. We establish a set of sufficient conditions that guarantee the permanence of the seasonally driven system. By conducting a numerical study on the seasonally forced model, we observe a myriad of phenomena manifesting the predator-prey dynamics. Notably, periodic solutions, higher periodic solutions, and bursting patterns emerge, alongside intriguing chaotic dynamics. Specifically, seasonal variations of the predator-taxis sensitivity and hunting cooperation can lead to the extinction of prey species and even the control of chaotic (higher periodic) solutions through the generation of a simple periodic solution. Remarkably, the seasonal forcing has the capacity to govern the chaotic behavior, leading to an exceptionally quasi-periodic arrangement in both prey and predator populations.

Impact of a school-based nutrition educational intervention on knowledge related to iron deficiency anaemia in rural Karnataka, India: A mixed methods pre-post interventional study.

OBJECTIVE: To understand the extent to which adolescent awareness about anaemia and anaemia prevention can be changed by nutrition messages received at school. DESIGN: Mixed-methods pre-post intervention study. SETTING: Three government schools in Bagalkot, Belagavi and Raichur districts of Karnataka, India. POPULATION: Students of grade six and seven and teachers involved in implementing the intervention. METHODS: An educational intervention was co-developed by school teachers and nutrition experts using locally adapted resource materials that consisted of lectures, role play and practical demonstrations. Seven half-hour educational sessions were delivered by school teachers over 7 weeks to 455 students. Pre- and post-intervention tests measured changes in adolescents' knowledge about anaemia. Semi-structured in-depth interviews with teachers and focus groups with students explored their reactions to the intervention. MAIN OUTCOME MEASURES: Knowledge score related to anaemia. RESULTS: The percentage of children with correct scores increased by 7.3-49.0 percentage points for the tested questions after implementation of the intervention. The mean knowledge score increased by 3.67 ± 0.17 (p < 0.01). During interviews, teachers and students highlighted high acceptance of the intervention and materials, an increase in awareness, a positive attitude towards changing behaviour around diet, an increase in the demand for iron and folic acid supplements and improved sharing of messages learned with peers and families. Challenges expressed included need for further training, time limitations and hesitancy in teaching about menstruation and pregnancy. CONCLUSIONS: Educational interventions carried out for adolescents by teachers in schools are effective in improving awareness and attitude related to anaemia and its prevention.

Three finger toxins of elapids: structure, function, clinical applications and its inhibitors.

The WHO lists snakebite as a "neglected tropical disease". In tropical and subtropical areas, envenoming is an important public health issue. This review article describes the structure, function, chemical composition, natural inhibitors, and clinical applications of Elapids' Three Finger Toxins (3FTX) using scientific research data. The primary venomous substance belonging to Elapidae is 3FTX, that targets nAChR. Three parallel ß-sheets combine to create 3FTX, which has four or five disulfide bonds. The three primary types of 3FTX are short-chain, long-chain, and nonconventional 3FTX. The functions of 3FTX depend on the specific toxin subtype and the target receptor or ion channel. The well-known effect of 3FTX is probably neurotoxicity because of the severe consequences of muscular paralysis and respiratory failure in snakebite victims. 3FTX have also been studied for their potential clinical applications. α-bungarotoxin has been used as a molecular probe to study the structure and function of nAChRs (Nicotinic Acetylcholine Receptors). Acid-sensing ion channel (ASIC) isoforms 1a and 1b are inhibited by Mambalgins, derived from Black mamba venom, which hinders their function and provide an analgesic effect. α- Cobra toxin is a neurotoxin purified from Chinese cobra (Naja atra) binds to nAChR at the neuronal junction and causes an analgesic effect for moderate to severe pain. Some of the plants and their compounds have been shown to inhibit the activity of 3FTX, and their mechanisms of action are discussed.

System Biology Investigation Revealed Lipopolysaccharide and Alcohol-Induced Hepatocellular Carcinoma Resembled Hepatitis B Virus Immunobiology and Pathogenesis.

Hepatitis B infection caused by the hepatitis B virus is a life-threatening cause of liver fibrosis, cirrhosis, and hepatocellular carcinoma. Researchers have produced multiple in vivo models for hepatitis B virus (HBV) and, currently, there are no specific laboratory animal models available to study HBV pathogenesis or immune response; nonetheless, their limitations prevent them from being used to study HBV pathogenesis, immune response, or therapeutic methods because HBV can only infect humans and chimpanzees. The current study is the first of its kind to identify a suitable chemically induced liver cirrhosis/HCC model that parallels HBV pathophysiology. Initially, data from the peer-reviewed literature and the GeneCards database were compiled to identify the genes that HBV and seven drugs (acetaminophen, isoniazid, alcohol, D-galactosamine, lipopolysaccharide, thioacetamide, and rifampicin) regulate. Functional enrichment analysis was performed in the STRING server. The network HBV/Chemical, genes, and pathways were constructed by Cytoscape 3.6.1. About 1546 genes were modulated by HBV, of which 25.2% and 17.6% of the genes were common for alcohol and lipopolysaccharide-induced hepatitis. In accordance with the enrichment analysis, HBV activates the signaling pathways for apoptosis, cell cycle, PI3K-Akt, TNF, JAK-STAT, MAPK, chemokines, NF-kappa B, and TGF-beta. In addition, alcohol and lipopolysaccharide significantly activated these pathways more than other chemicals, with higher gene counts and lower FDR scores. In conclusion, alcohol-induced hepatitis could be a suitable model to study chronic HBV infection and lipopolysaccharide-induced hepatitis for an acute inflammatory response to HBV.

Anti-Dengue Activity of Lipophilic Fraction of Ocimum basilicum L. Stem.

Ocimum basilicum L. is used to cure many types of fever in traditional medicine. This study aims to explore the antiviral activity of the lipophilic fraction of the stem of O. basilicum (LFOB) against dengue virus (DENV) and chikungunya virus (CHIKV). The LFOB was analyzed using GC-FID and GC-MS. The antiviral activity of LFOB was studied using the Vero CCL-81 cell line. The cytotoxicity assay was performed using 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). In vitro antiviral activity and FFU assay were used to determine and confirm antiviral activity against DENV and CHIKV. Twenty-six compounds were identified in LFOB using GC/MS. The most abundant compounds were ß-sitosterol (22.9%), stigmasterol (18.7%), and campesterol (12.9%). Significant reduction in DENV titre was observed under pre- and post-infection treatment conditions at a concentration of 3.125 µg/mL, but no anti-CHIKV activity was observed. Our earlier and the present AutoDock-Vina-based in silico docking study revealed that ß-sitosterol and stigmasterol could form strong interactions with the DENV E glycoprotein and DENV RdRp domain, respectively. Our findings suggest that LFOB can inhibit DENV infection and might act as a potent prophylactic/therapeutic agent against DENV-2. In silico results suggested that ß-sitosterol and stigmasterol may block the viral entry by inhibiting the fusion process and viral replication respectively.

In Silico Study on the Interactions, Molecular Docking, Dynamics and Simulation of Potential Compounds from Withania somnifera (L.) Dunal Root against Cancer by Targeting KAT6A.

Cancer is characterized by the abnormal development of cells that divide in an uncontrolled manner and further take over the body and destroy the normal cells of the body. Although several therapies are practiced, the demand and need for new therapeutic agents are ever-increasing because of issues with the safety, efficacy and efficiency of old drugs. Several plant-based therapeutics are being used for treatment, either as conjugates with existing drugs or as standalone formulations. Withania somnifera (L.) Dunal is a highly studied medicinal plant which is known to possess immunomodulatory activity as well as anticancer properties. The pivotal role of KAT6A in major cellular pathways and its oncogenic nature make it an important target in cancer treatment. Based on the literature and curated datasets, twenty-six compounds from the root of W. somnifera and a standard inhibitor were docked with the target KAT6A using Autodock vina. The compounds and the inhibitor complexes were subjected to molecular dynamics simulation (50 ns) using Desmond to understand the stability and interactions. The top compounds (based on the docking score of less than -8.5 kcal/mol) were evaluated in comparison to the inhibitor. Based on interactions at ARG655, LEU686, GLN760, ARG660, LEU689 and LYS763 amino acids with the inhibitor WM-8014, the compounds from W. somnifera were evaluated. Withanolide D, Withasomniferol C, Withanolide E, 27-Hydroxywithanone, Withanolide G, Withasomniferol B and Sitoindoside IX showed high stability with the residues of interest. The cell viability of human breast cancer MCF-7 cells was evaluated by treating them with W. Somnifera root extract using an MTT assay, which showed inhibitory activity with an IC50 value of 45 µg/mL. The data from the study support the traditional practice of W. somnifera as an anticancer herb.

Exploring the Potential of Phytocompounds for Targeting Epigenetic Mechanisms in Rheumatoid Arthritis: An In Silico Study Using Similarity Indexing.

Finding structurally similar compounds in compound databases is highly efficient and is widely used in present-day drug discovery methodology. The most-trusted and -followed similarity indexing method is Tanimoto similarity indexing. Epigenetic proteins like histone deacetylases (HDACs) inhibitors are traditionally used to target cancer, but have only been investigated very recently for their possible effectiveness against rheumatoid arthritis (RA). The synthetic drugs that have been identified and used for the inhibition of HDACs include SAHA, which is being used to inhibit the activity of HDACs of different classes. SAHA was chosen as a compound of high importance as it is reported to inhibit the activity of many HDAC types. Similarity searching using the UNPD database as a reference identified aglaithioduline from the Aglaia leptantha compound as having a ~70% similarity of molecular fingerprints with SAHA, based on the Tanimoto indexing method using ChemmineR. Aglaithioduline is abundantly present in the shell and fruits of A. leptantha. In silico studies with aglaithioduline were carried out against the HDAC8 protein target and showed a binding affinity of -8.5 kcal mol. The complex was further subjected to molecular dynamics simulation using Gromacs. The RMSD, RMSF, compactness and SASA plots of the target with aglaithioduline, in comparison with the co-crystallized ligand (SAHA) system, showed a very stable configuration. The results of the study are supportive of the usage of A. leptantha and A. edulis in Indian traditional medicine for the treatment of pain-related ailments similar to RA. Our study therefore calls for further investigation of A. leptantha and A. edulis for their potential use against RA by targeting epigenetic changes, using in vivo and in vitro studies.

Hepatitis C Virus NS3/4A Inhibition and Host Immunomodulation by Tannins from Terminalia chebula: A Structural Perspective.

Terminalia chebula Retz. forms a key component of traditional folk medicine and is also reported to possess antihepatitis C virus (HCV) and immunomodulatory activities. However, information on the intermolecular interactions of phytochemicals from this plant with HCV and human proteins are yet to be established. Thus, by this current study, we investigated the HCV NS3/4A inhibitory and host immune-modulatory activity of phytocompounds from T. chebula through in silico strategies involving network pharmacology and structural bioinformatics techniques. To start with, the phytochemical dataset of T. chebula was curated from biological databases and the published literature. Further, the target ability of the phytocompounds was predicted using BindingDB for both HCV NS3/4A and other probable host targets involved in the immune system. Further, the identified targets were docked to the phytochemical dataset using AutoDock Vina executed through the POAP pipeline. The resultant docked complexes with significant binding energy were subjected to 50 ns molecular dynamics (MD) simulation in order to infer the stability of complex formation. During network pharmacology analysis, the gene set pathway enrichment of host targets was performed using the STRING and Reactome pathway databases. Further, the biological network among compounds, proteins, and pathways was constructed using Cytoscape 3.6.1. Furthermore, the druglikeness, side effects, and toxicity of the phytocompounds were also predicted using the MolSoft, ADVERpred, and PreADMET methods, respectively. Out of 41 selected compounds, 10 were predicted to target HCV NS3/4A and also to possess druglike and nontoxic properties. Among these 10 molecules, Chebulagic acid and 1,2,3,4,6-Pentagalloyl glucose exhibited potent HCV NS3/4A inhibitory activity, as these scored a lowest binding energy (BE) of -8.6 kcal/mol and -7.7 kcal/mol with 11 and 20 intermolecular interactions with active site residues, respectively. These findings are highly comparable with Asunaprevir (known inhibitor of HCV NS3/4A), which scored a BE of -7.4 kcal/mol with 20 key intermolecular interactions. MD studies also strongly suggest that chebulagic acid and 1,2,3,4,6-Pentagalloyl glucose as promising leads, as these molecules showed stable binding during 50 ns of production run. Further, the gene set enrichment and network analysis of 18 protein targets prioritized 10 compounds and were predicted to potentially modulate the host immune system, hemostasis, cytokine levels, interleukins signaling pathways, and platelet aggregation. On overall analysis, this present study predicts that tannins from T. chebula have a potential HCV NS3/4A inhibitory and host immune-modulatory activity. However, further experimental studies are required to confirm the efficacies.

Diversity of rotavirus genotypes circulating in children < 5 years of age hospitalized for acute gastroenteritis in India from 2005 to 2016: analysis of temporal and regional genotype variation.

BACKGROUND: From 2016, the Government of India introduced the oral rotavirus vaccine into the national immunization schedule. Currently, two indigenously developed vaccines (ROTAVAC, Bharat Biotech; ROTASIIL, Serum Institute of India) are included in the Indian immunization program. We report the rotavirus disease burden and the diversity of rotavirus genotypes from 2005 to 2016 in a multi-centric surveillance study before the introduction of vaccines. METHODS: A total of 29,561 stool samples collected from 2005 to 2016 (7 sites during 2005-2009, 3 sites from 2009 to 2012, and 28 sites during 2012-2016) were included in the analysis. Stools were tested for rotavirus antigen using enzyme immunoassay (EIA). Genotyping was performed on 65.8% of the EIA positive samples using reverse transcription- polymerase chain reaction (RT-PCR) to identify the G (VP7) and P (VP4) types. Multinomial logistic regression was used to quantify the odds of detecting genotypes across the surveillance period and in particular age groups. RESULTS: Of the 29,561 samples tested, 10,959 (37.1%) were positive for rotavirus. There was a peak in rotavirus positivity during December to February across all sites. Of the 7215 genotyped samples, G1P[8] (38.7%) was the most common, followed by G2P[4] (12.3%), G9P[4] (5.8%), G12P[6] (4.2%), G9P[8] (4%), and G12P[8] (2.4%). Globally, G9P[4] and G12P[6] are less common genotypes, although these genotypes have been reported from India and few other countries. There was a variation in the geographic and temporal distribution of genotypes, and the emergence or re-emergence of new genotypes such as G3P[8] was seen. Over the surveillance period, there was a decline in the proportion of G2P[4], and an increase in the proportion of G9P[4]. A higher proportion of mixed and partially typed/untyped samples was also seen more in the age group 0-11 months. CONCLUSIONS: This 11 years surveillance highlights the high burden of severe rotavirus gastroenteritis in Indian children < 5 years of age before inclusion of rotavirus vaccines in the national programme. Regional variations in rotavirus epidemiology were seen, including the emergence of G3P[8] in the latter part of the surveillance. Having pre-introduction data is important to track changing epidemiology of rotaviruses, particularly following vaccine introduction.

Functional studies of Plasmodium falciparum putative SURF1 in Saccharomyces cerevisiae.

BACKGROUND AND OBJECTIVES: The mitochondrial electron transport chain (mtETC) of Plasmodium falciparum is an important drug target. Identification and functional validation of putative mitochondrial proteins of the mtETC is critical for drug development. Many of the regulatory subunits and assembly factors of cytochrome c oxidase readily identifiable in humans and yeast are missing in P. falciparum. Here, we describe our efforts to identify and validate the function of putative Pfsurf1, a key assembly factor of complex IV of the mtETC. METHODS: Multiple sequence alignment of SURF 1/Shy 1 was carried out in Clustal X 2.1. Phylogenetic tree was constructed using "Draw tree" option in Clustal X, and was analyzed using interactive Tree of Life software. To identify the conserved sequences, domain search was done using Jalview version 2.8.2 (BLOSUM 62 scoring). The haploid Saccharomyces cerevisiae strain (BY4741) containing the null allele shy1 (Orf: YGR112w) (shy1::Kan) was complemented with putative Pfsurf1 to study its ability to rescue the growth defect. RESULTS: Similarity searches of PfSURF1-like protein in the Pfam shows statistically significant E = 4.7e-10 match to SURF1 family. Sequence alignment of PfSURF1 with other SURF1-like proteins reveals the conservation of transmembrane domains, α-helices and ß-pleated sheets. Phylogenetic analysis clusters putative PfSURF1 with apicomplexan SURF1-like proteins. Yeast complementation studies show that Pfsurf1 can partially rescue the yeast shy1 mutant, YGR112w. INTERPRETATION & CONCLUSION: Bioinformatics and complementation studies in yeast show that P. falciparum's SURF1 is the functional ortholog of human SURF1 and yeast Shy1.

Risk Factors for Detection, Survival, and Growth of Antibiotic-Resistant and Pathogenic Escherichia coli in Household Soils in Rural Bangladesh.

Soils in household environments in low- and middle-income countries may play an important role in the persistence, proliferation, and transmission of Escherichia coli Our goal was to investigate the risk factors for detection, survival, and growth of E. coli in soils collected from household plots. E. coli was enumerated in soil and fecal samples from humans, chickens, and cattle from 52 households in rural Bangladesh. Associations between E. coli concentrations in soil, household-level risk factors, and soil physicochemical characteristics were investigated. Susceptibility to 16 antibiotics and the presence of intestinal pathotypes were evaluated for 175 E. coli isolates. The growth and survival of E. coli in microcosms using soil collected from the households were also assessed. E. coli was isolated from 44.2% of the soil samples, with an average of 1.95 log10 CFU/g dry soil. Soil moisture and clay content were associated with E. coli concentrations in soil, whereas no household-level risk factor was significantly correlated. Antibiotic resistance and pathogenicity were common among E. coli isolates, with 42.3% resistant to at least one antibiotic, 12.6% multidrug resistant (≥3 classes), and 10% potentially pathogenic. Soil microcosms demonstrate growth and/or survival of E. coli, including an enteropathogenic extended-spectrum beta-lactamase (ESBL)-producing isolate, in some, but not all, of the household soils tested. In rural Bangladesh, defined soil physicochemical characteristics appear more influential for E. coli detection in soils than household-level risk factors. Soils may act as reservoirs in the transmission of antibiotic-resistant and potentially pathogenic E. coli and therefore may impact the effectiveness of water, sanitation, and hygiene interventions.IMPORTANCE Soil may represent a direct source or act as an intermediary for the transmission of antibiotic-resistant and pathogenic Escherichia coli strains, particularly in low-income and rural settings. Thus, determining risk factors associated with detection, growth, and long-term survival of E. coli in soil environments is important for public health. Here, we demonstrate that household soils in rural Bangladesh are reservoirs for antibiotic-resistant and potentially pathogenic E. coli strains and can support E. coli growth and survival, and defined soil physicochemical characteristics are drivers of E. coli survival in this environment. In contrast, we found no evidence that household-level factors, including water, sanitation, and hygiene indicators, were associated with E. coli contamination of household soils.

Vibrio cholerae O1 El Tor variant and emergence of Haitian ctxB variant in the strains isolated from South India.

Cholera still continues to be an important cause of human infection, especially in developing countries that lack access to safe drinking water and proper sanitation. In the present study, we report the emergence of new variant form of V. cholerae O1 El Tor biotype with a novel mutation in ctxB in strains isolated from various outbreaks during 2010-2014 in Belgaum situated in north-west Karnataka, India. A total of 14 occurrences of cholera were documented from Belgaum Division of North Karnataka during the 4-year period from 2010 to 2014. All the V. cholerae O1 isolates were subjected to DAMA PCR to detect the three different allelic subtypes of ctxB and PCR-based detection of virulent genes, and subsequently, 14 strains (one strain from each outbreak or sporadic case) were subjected to ctxB gene sequence and pulsed-field gel electrophoresis (PFGE) analysis. A total of 54 V. cholerae O1 strains were obtained of which 21 strains isolated during 2010-2011 had classical ctxB and remaining 33 strains isolated during 2012-2014 belonged to Haitian variant. In the cluster analysis, the PFGE profiles were divided into clades A with and B. Clade A contained eight strains with 94 % similarity and Haitian type of ctxB. Clade B contained six strains and had Haitian type of ctxB except one with classical ctxB. To the best of our knowledge, this is the first report of the Haitian variant of V. cholerae O1 Ogawa causing outbreaks and sporadic cases of cholera in South India.

In-silico analysis of gymnemagenin from Gymnema sylvestre (Retz.) R.Br. with targets related to diabetes.

Diabetes is a metabolic disorder characterized by higher than normal glucose in the blood. Most oral hypoglycemic drugs available in market produce adverse side effects which have resulted in continued search for new therapeutic agents with little or no side effects. Herbal drugs are considered relatively safer alternatives and Gymnema sylvestre is one of the most well established natural remedy for diabetes and is traded worldwide under several brands. In the present study an attempt has been made to use in silico techniques to understand and predict the drug likeliness of gymnemagenin, one of the key constituents of G. sylvestre against 15 proteins having key role in carbohydrate metabolism. Gymnemagenin was found to dock well with crystallographic structures of 7 of the 15 selected targets and was found even better than the two known clinically used antidiabetic compounds, repaglinide and sitagliptin taken in the study for comparison. Gymnemagenin therefore can be considered further for development into a potent anti-diabetic drug.

Genotypic and phenotypic characterization of Escherichia coli isolates from feces, hands, and soils in rural Bangladesh via the Colilert Quanti-Tray System.

The increased awareness of the role of environmental matrices in enteric disease transmission has resulted in the need for rapid, field-based methods for fecal indicator bacteria and pathogen detection. Evidence of the specificity of ß-glucuronidase-based assays for detection of Escherichia coli from environmental matrices relevant to enteric pathogen transmission in developing countries, such as hands, soils, and surfaces, is limited. In this study, we quantify the false-positive rate of a ß-glucuronidase-based E. coli detection assay (Colilert) for two environmental reservoirs in Bangladeshi households (hands and soils) and three fecal composite sources (cattle, chicken, and humans). We investigate whether or not the isolation source of E. coli influences phenotypic and genotypic characteristics. Phenotypic characteristics include results of biochemical assays provided by the API-20E test; genotypic characteristics include the Clermont phylogroup and the presence of enteric and/or environmental indicator genes sfmH, rfaI, and fucK. Our findings demonstrate no statistically significant difference in the false-positive rate of Colilert for environmental compared to enteric samples. E. coli isolates from all source types are genetically diverse, representing six of the seven phylogroups, and there is no difference in relative frequency of phylogroups between enteric and environmental samples. We conclude that Colilert, and likely other ß-glucuronidase-based assays, is appropriate for detection of E. coli on hands and in soils with low false-positive rates. Furthermore, E. coli isolated from hands and soils in Bangladeshi households are diverse and indistinguishable from cattle, chicken, and human fecal isolates, using traditional biochemical assays and phylogrouping.

Status of hepatitis B infection - a decade after hepatitis B vaccination of susceptible Nicobarese, an indigenous tribe of Andaman & Nicobar (A&N) islands with high hepatitis B endemicity.

BACKGROUND & OBJECTIVES: Andaman and Nicobar Islands of India, home to six primitive tribes, constituting about 10 per cent of the total population of these Islands have been detected with high endemicity of hepatitis B infection. During 2000, a total of 936 individuals ≤ 45 yr, negative for hepatitis B surface antigen (HBsAg) and antibody anti-HBs were vaccinated with three doses of a recombinant DNA hepatitis B vaccine in two villages of Car Nicobar Islands. The present study was undertaken to evaluate the impact of the hepatitis B vaccination with respect to the persistence of antibodies and incidence of new infections, prevalence of surface gene mutations among the Nicobarese community in the two villages ten years after hepatitis B vaccination. METHODS: Follow up samples were collected from 211 individuals who had received three doses of vaccine ten years back and from a control group of 515 non-vaccinated individuals. The HBsAg, anti-HBs and anti-HBc assay results were compared among vaccinated and non-vaccinated groups. HBV DNA was extracted and sequenced from all the samples for detection of mutation. Genotyping and serotyping of the viruses were performed. RESULTS: The results showed that 85.3 per cent of the vaccinated persons retained protective level of antibodies and among the non-vaccinated individuals, 54.2 per cent showed presence of anti-HBs indicating an exposure to the infection. The overall HBsAg positivity among the studies Nicobarese individuals was reduced to 7.4 per cent after 10 years of vaccination. Anti-HBc was positive in 60.6 and 57 per cent among the vaccinated and non-vaccinated individuals, respectively. Overall breakthrough infection of 8.5 per cent was detected among the vaccinated individuals. The predominant genotype and serotype circulating among these tribal populations were D and ayw3, respectively. INTERPRETATION & CONCLUSIONS: The results of this study showed an overall reduction in the pool of HBsAg carriers because of the vaccination which helped in reducing the HBsAg carrier rate among the non-vaccinated also, probably due to an increase in herd immunity and reduction in the source of infection. Further studies need to be done to evaluate long term benefits of hepatitis B vaccination among these tribes.

Tribes in Karnataka: Status of health research.

The south Indian State of Karnataka, once part of several kingdoms and princely states of repute in the Deccan peninsula, is rich in its historic, cultural and anthropological heritage. The State is the home to 42,48,987 tribal people, of whom 50,870 belong to the primitive group. Although these people represent only 6.95 per cent of the population of the State, there are as many as 50 different tribes notified by the Government of India, living in Karnataka, of which 14 tribes including two primitive ones, are primarily natives of this State. Extreme poverty and neglect over generations have left them in poor state of health and nutrition. Unfortunately, despite efforts from the Government and non-Governmental organizations alike, literature that is available to assess the state of health of these tribes of the region remains scanty. It is however, interesting to note that most of these tribes who had been original natives of the forests of the Western Ghats have been privy to an enormous amount of knowledge about various medicinal plants and their use in traditional/folklore medicine and these practices have been the subject matter of various scientific studies. This article is an attempt to list and map the various tribes of the State of Karnataka and review the studies carried out on the health of these ethnic groups, and the information obtained about the traditional health practices from these people.

Prevalence of mutations in basal core promoter and precore region of hepatitis B virus in vaccinated and nonvaccinated individuals of the aboriginal Nicobarese tribe of Car Nicobar Island, India.

The aim of this study was to explore the prevalence of basal core promoter (BCP) and precore gene (PC) mutations in hepatitis B virus (HBV) isolates among the Nicobarese tribe and their relationship with genotypes and HBeAg status. A total of 726 blood samples were collected from two villages of the Car Nicobar Island where mass vaccination was performed in the year 2000. HBV DNA was isolated and the BCP and PC regions were amplified and sequenced directly. The samples positive for HBV DNA were tested for HBsAg, HBeAg and anti-HBe. Among the 211 and 515 samples collected from vaccinated and nonvaccinated persons, 16 and 82 were positive for HBV DNA, respectively. Among the vaccinated individuals, only 1 had a mutation in both the BCP and PC gene. Among the nonvaccinated subjects, 3 (4.5%) had an A1762T mutation, 8 (12.1%) had a G1764A mutation, 11 (16.7%) had a G1896A mutation and 4 (6.1%) had a G1899A mutation. The HBeAg-negative subjects had a significantly higher frequency of BCP and PC mutations than the HBeAg-positive subjects. The prevalence of a PC mutation was higher than that of a BCP mutation. The present study stresses the need for the continuous surveillance of subjects with BCP and PC mutations, as the mutations may contribute to the progression of liver disease.